Cytoplasmic mislocalization of overexpressed FOXF1 is associated with the malignancy and metastasis of colorectal adenocarcinomas

Pang Kuo Lo, Ji Shin Lee, Hexin Chen, David Reisman, Franklin G. Berger, Saraswati Sukumar

Research output: Contribution to journalArticle

Abstract

Our previous studies have revealed that the human FOXF1 gene, encoding a transcription factor member of the forkhead box (FOX) family, functions as a tumor suppressor and its expression is frequently silenced in breast cancer via DNA hypermethylation. Moreover, we recently reported that FOXF1 expression is preferentially silenced in colorectal cancer cell lines with inactive p53 and knockdown of FOXF1 caused genomic instability in FOXF1-expressing colorectal cancer cells with a defect in the p53-p21WAF1 checkpoint, suggesting that FOXF1 plays a key role in colorectal tumorigenesis. Given that the in vivo role of FOXF1 in colorectal cancer remains unknown, the study here was aimed at delineating the clinical relevance of FOXF1 in colorectal adenocarcinomas. To characterize FOXF1 protein expression in colorectal cancer, designed tissue microarrays, comprising 50 cases of primary colorectal adenocarcinoma paired with matched adjacent normal tissue, were utilized in the immunohistochemistry (IHC) study. The IHC results showed that for adjacent normal colorectal tissue, the FOXF1 protein was only detected in stroma, not in epithelium, with either cytoplasmic staining (70% of total cases) or a mix of cytoplasmic and nuclear staining (6%). In contrast, for colorectal adenocarcinomas, FOXF1 staining was predominately identified in the cytoplasm of tumor epithelial cells (40% of total cases) and tumor-associated stromal cells of some cases (10%) also exhibited FOXF1 positivity in their cytoplasm. Cytoplasmic FOXF1 protein expression in tumor epithelial cells positively correlated with the histologic grade, depth of invasion, stage and lymphatic metastasis of colorectal adenocarcinomas (p

Original languageEnglish (US)
Pages (from-to)262-269
Number of pages8
JournalExperimental and Molecular Pathology
Volume94
Issue number1
DOIs
StatePublished - Feb 2013

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Tumors
Colorectal Neoplasms
Adenocarcinoma
Neoplasm Metastasis
Tissue
Staining and Labeling
Neoplasms
Cytoplasm
Epithelial Cells
Immunohistochemistry
Cells
Forkhead Transcription Factors
Lymphatic Metastasis
Proteins
Gene encoding
Genomic Instability
Microarrays
Stromal Cells
Carcinogenesis
Transcription Factors

Keywords

  • Colorectal cancer
  • Cytoplasmic mislocalization
  • FOXF1
  • Immunohistochemistry
  • Tissue microarrays
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Pathology and Forensic Medicine

Cite this

Cytoplasmic mislocalization of overexpressed FOXF1 is associated with the malignancy and metastasis of colorectal adenocarcinomas. / Lo, Pang Kuo; Lee, Ji Shin; Chen, Hexin; Reisman, David; Berger, Franklin G.; Sukumar, Saraswati.

In: Experimental and Molecular Pathology, Vol. 94, No. 1, 02.2013, p. 262-269.

Research output: Contribution to journalArticle

Lo, Pang Kuo ; Lee, Ji Shin ; Chen, Hexin ; Reisman, David ; Berger, Franklin G. ; Sukumar, Saraswati. / Cytoplasmic mislocalization of overexpressed FOXF1 is associated with the malignancy and metastasis of colorectal adenocarcinomas. In: Experimental and Molecular Pathology. 2013 ; Vol. 94, No. 1. pp. 262-269.
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